In vitro effect of D-myo-inositol 1,2,6-trisphosphate (PP-56) on aggregation of platelets from normal and diabetic rats: relationship to malondialdehyde release and phosphoinositide pathway.

In the present study, we investigated the in vitro effects of D-myo-inositol 1,2,6-trisphosphate (PP-56) on platelets from normal and streptozotocin-induced diabetic rats. PP-56 markedly inhibited aggregation, in a dose-related manner, when added in vitro, more efficiently with thrombin- than with ADP-induced aggregation and, after 90 min incubation, more in diabetic than in normal platelets. The PP-56 platelet inhibitory effect seems to be related to its phosphate content. PP-56 blocked the release of malondialdehyde from erythrocytes, but to the same extent in normal and diabetic rats. PP-56, after 20 min incubation, restored the platelet phosphoinositide turnover, which was significantly modified in diabetic rats. This last observation could explain at least part of the specificity of PP-56 for normalizing platelet aggregation in diabetic animals after long-term administration in vivo.